distal convoluted tubule

The Dietary Approach to Stop Hypertension (DASH) diet, with its low sodium and high potassium content, acts like a diuretic by reducing sodium reabsorption in the kidney's distal convoluted tubule but without the side effects. Previous studies based on animal models didn't explore changes in human ion channel proteins. Recent insights into urinary extracellular vesicles (uEVs) suggest they reflect kidney tissue and physiological modifications. In our inpatient study, we shifted hypertensive volunteers from an American diet to the DASH diet, examining changes in those with stage 1 untreated hypertension...

PURPOSE OF REVIEW: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules. RECENT FINDINGS: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates...

The kidneys are crucial for maintaining Mg2+ homeostasis. Along the proximal tubule and thick ascending limb, Mg2+ is reabsorbed paracellularly, while along the distal convoluted tubule (DCT), Mg2+ is reabsorbed transcellularly via transient receptor potential melastatin 6 (TRPM6). TRPM6 and other renal transporter expressions are regulated by sex hormones. To investigate renal Mg2 handling, we have developed sex-specific computational models of electrolyte transport along rat superficial nephron. Model simulations indicated that along the proximal tubule and thick ascending limb, Mg2+ and Na+ transport occur parallelly, but they are dissociated along the DCT...

BACKGROUND: Renal ischemia-reperfusion injury (RIRI) is an inevitable complication in the process of kidney transplantation and lacks specific therapy. The study aims to determine the underlying mechanisms of RIRI to uncover a promising target for efficient renoprotection. METHOD: Four bulk RNA-seq datasets including 495 renal samples of pre- and post-reperfusion were collected from the GEO database. The machine learning algorithms were utilized to ascertain pivotal endoplasmic reticulum stress genes...

BACKGROUND: Potassium (K+ )-deficient diets, typical of modern processed foods, increase blood pressure (BP) and NaCl sensitivity. A K+ -dependent signaling pathway in the kidney distal convoluted tubule, coined the K+ switch, that couples extracellular K+ sensing to activation of the thiazide-sensitive NaCl cotransporter (NCC) and NaCl retention has been implicated, but causality has not been established. METHODS: To test the hypothesis that small, physiological changes in plasma K+ (PK+ ) are translated to BP through the switch pathway, a genetic approach was used to activate the downstream switch kinase, SPAK (SPS1-related proline/alanine-rich kinase), within the distal convoluted tubule...

Efferent sympathetic nerve fibers regulate several renal functions activating norepinephrine receptors on tubular epithelial cells. Of the beta-adrenoceptors (β-ARs), we previously demonstrated the renal expression of β3-AR in the thick ascending limb (TAL), the distal convoluted tubule (DCT), and the collecting duct (CD), where it participates in salt and water reabsorption. Here, for the first time, we reported β3-AR expression in the CD intercalated cells (ICCs), where it regulates acid-base homeostasis...

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BACKGROUND: The thiazide-sensitive sodium chloride cotransporter (NCC) is the major apical sodium transporter located in the mammalian renal distal convoluted tubule (DCT). The amount of sodium reabsorbed in the DCT through NCC plays an important role in the regulation of extracellular fluid volume and blood pressure. Dopamine and its receptors constitute a renal antihypertensive system in mammals. The disruption of Drd4 in mice causes kidney-related hypertension. However, the pathogenesis of D4R-deficiency associated hypertension is not well documented...

No abstract text is available yet for this article.

UNLABELLED: Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited. Here, we optimized an extracellular flux analysis (EFA) to study mitochondrial respiration and energy metabolism using microdissected mouse renal tubule segments...

A flock of 48 sheep in Argentina grazing on a pasture of hybrid Urochloa (formerly Brachiaria ) Mulato II ( Urochloa ruziziensis  ×  Urochloa decumbens  ×  Urochloa brizantha ) developed facial dermatitis, severe jaundice, and weakness after brief physical activity. Blood biochemistry of 3 animals revealed azotemia, elevated aspartate aminotransferase activity, and increased direct, indirect, and total bilirubin concentrations. The urine was markedly turbid and contained large concentrations of bile pigments and protein...

Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: type 3 Bartter and Gitelman diseases, Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis...

The Na+ -Cl- cotransporter (NCC; SLC12A3) is a highly regulated integral membrane protein that is known to exist as 3 splice variants in primates. Its primary role in the kidney is to mediate the cosymport of Na+ and Cl- across the apical membrane of the distal convoluted tubule. Through this role and the involvement of other ion transport systems, NCC allows the systemic circulation to reclaim a fraction of the ultrafiltered Na+ , K+ , Cl- and Mg+ loads in exchange for Ca2+ and HCO3 - . The physiological relevance of the Na+ -Cl- cotransport mechanism in human is illustrated by the several abnormalities that result from NCC inactivation through the administration of thiazides or in the setting of hereditary disorders...

Aldosterone is responsible for maintaining volume and potassium homeostasis. Although high salt consumption should suppress aldosterone production, individuals with hyperaldosteronism lose this regulation, leading to a state of high aldosterone despite dietary sodium consumption. The present study examines the effects of elevated aldosterone, with or without high salt consumption, on the expression of key Na+ transporters and remodelling in the distal nephron. Epithelial sodium channel (ENaC) α-subunit expression was increased with aldosterone regardless of Na+ intake...

KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal excretion by modulating the activity of the Na+ -Cl- cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low potassium diet...

BACKGROUND: Potassium regulates the WNK (with no lysine kinase)-SPAK (STE20/SPS1-related proline/alanine-rich kinase) signaling axis, which in turn controls the phosphorylation and activation of the distal convoluted tubule thiazide-sensitive NCC (sodium-chloride cotransporter) for sodium-potassium balance. Although their roles in the kidney have not been investigated, it has been postulated that Cab39 (calcium-binding protein 39) or Cab39l (Cab39-like) is required for SPAK/OSR1 (oxidative stress response 1) activation...

BACKGROUND: Most cases of autosomal dominant polycystic kidney disease (ADPKD) are caused by mutations in PKD1 or PKD2. Currently, the mechanism for renal cyst formation remains unclear. Aqp2+ progenitor cells (AP) (re)generate ≥5 cell types including principal cells (PC) and intercalated cells (IC) in the late distal convoluted tubules (DCT2), connecting tubules (CNT), and collecting ducts (CD). METHODS: Here, we tested whether Pkd2 deletion in AP and their derivatives at different developmental stages is sufficient to induce PKD...

SIGNIFICANCE STATEMENT: High-resolution single-nucleus RNA-sequencing data indicate a clear separation between primary sites of calcium and magnesium handling within distal convoluted tubule (DCT). Both DCT1 and DCT2 express Slc12a3, but these subsegments serve distinctive functions, with more abundant magnesium-handling genes along DCT1 and more calcium-handling genes along DCT2. The data also provide insight into the plasticity of the distal nephron-collecting duct junction, formed from cells of separate embryonic origins...

Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease, with discrete roles for intracellular, urinary, interstitial, and serum uromodulin. Among them, uromodulin modulates renal sodium handling through the regulation of tubular sodium transporters that reabsorb sodium and are targeted by diuretics, such as the loop diuretic-sensitive Na+-K+-2Cl- cotransporter type 2 (NKCC2) and the thiazide-sensitive Na+/Cl- cotransporter (NCC)...

In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq)...